There is increasing evidence in the scientific literature that there are adverse health effects associated with levels of ambient air pollution that fall within the current standards, especially for populations with chronic respiratory diseases. Children and adults with cystic fibrosis (CF) are an at-risk population for which the health effects of ambient air pollution have not previously been investigated. Identifying environmental risk factors for the progression of pulmonary disease in the cystic fibrosis population may contribute to better understanding of this complex heterogeneous nature of this disease. Our objective is to assess and clarify the association between air pollutants and CF lung health and mortality among U.S. CF patients. Information concerning the impact of environmental factors on cystic fibrosis is limited. We recently completed a preliminary cohort study to assess the impact of air pollutants in cystic fibrosis. The study included patients over the age of 6 years enrolled in the Cystic Fibrosis Foundation National Patient Registry in 1999 and 2000. Exposure was assessed by linking air pollution values from the Aerometric Information Retrieval System with patients' home zip code. We found that after adjusting for confounders, a 10 [unreadable]g/m3 rise in course particulate matter (PM10) and fine particulate matter (PM2.5) was associated with an 8% (95% CI 2-15%) and 21% (7-33%) increase in the odds of two or more exacerbations, respectively; a 10ppb rise in ozone was associated with a 10% (3-17%) increase in odds of two or more exacerbations. We also found that for every increase in PM2.5 of 10 [unreadable]g/m3, there was an associated fall in forced expiratory volume in 1 second (FEV1) of 24 ml (7 - 40) after adjusting for confounders. Given this finding, we evaluating the impact of longer term exposure to ambient air pollution on lung function and mortality in CF. We found a strong association between ambient air pollution and lung function as measured by FEV1. Increased PM2.5 and PM10 was associated with lower lung function. Given this data, it is critical to understand whether air pollution affects lung growth in CF patients, given the relationship between lung function and survival in CF. We propose to first model lung growth in CF based on mixed effects multivariate regression models of FEV1 and forced vital capacity (FVC) in children ages 6-18 with cystic fibrosis from 1994-2005. We will then assess the impact of ambient air pollution (as assessed by average annual exposure) on lung growth. Lastly, we propose evaluating the impact of different methodologies of exposure (ambient air pollution) modeling on the impact of air pollution on lung growth in CF. As CF researchers search for gene modifiers in CF disease to better understand the pathophysiology of CF lung disease and identify new potential therapies, it is critical to understand how important environmental exposures are in the course of the disease. Our proposal work may contribute to a better understanding of the role of environmental factors on cystic fibrosis (CF) outcome and prognosis and also could add to the growing body of evidence regarding the health effects of air pollutants on susceptible and at risk populations. Our proposal will also enhance our understanding of lung growth in CF and represents the initial phase of a program to understand environmental effects on CF lung disease. [unreadable] [unreadable] [unreadable]